tbuckley/cabot-search huggingface dataset:
Functional Impairment in Individuals With Prodromal or Unrecognized Parkinson Disease
Authors: Cameron Miller-Patterson, Jesse Y. Hsu, Allison W. Willis, Ali G. Hamedani
Journal: JAMA Neurology (2022)

Importance Daily functioning in individuals with prodromal Parkinson disease requires more detailed description. Objective To evaluate whether functional limitations exist in individuals with Parkinson disease prior to diagnosis compared with the general population. Design, Setting, and Participants This case-control study used Medicare-linked data from the National Health and Aging Trends Study (NHATS), a longitudinal survey in the US, for a random subsample of Medicare beneficiaries aged 65 years or older, with Black and older individuals oversampled by design. Patients with incident Parkinson disease were defined as having 2 or more Medicare diagnoses from January 2011 to December 2017, with Medicare eligibility 2 or more consecutive years prior to the first diagnosis. Controls were defined as individuals with Medicare eligibility at a baseline year and 2 or more years prior, with no Parkinson disease diagnosis. Analyses were conducted from November 2021 to June 2022. Exposures Responses to survey questions addressing dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision. Main Outcome and Measures Associations between survey responses and Parkinson disease diagnosis in the first year of diagnosis (baseline) and up to 3 years prior to diagnosis (ie, during the prodromal phase) were examined using logistic regression. Results A total of 6674 participants were included. The participant numbers and case prevalence each year varied from 3492 to 5049 and from 700 to 1180 per 100 000 population, respectively. The median age groups were 75 to 79 years and 80 to 84 years, and the percentage of females varied from 48.21% (27 of 56 cases) to 59.98% (2079 of 3466 controls) across all years, with similar proportions among cases and controls. Individuals with prodromal Parkinson disease were less likely to report being able to walk 6 blocks (odds ratio [OR], 0.34; 95% CI, 0.15-0.82), stand independently from a kneeling position (OR, 0.30; 95% CI, 0.11-0.85), or lift a heavy object above one’s head (OR, 0.36; 95% CI, 0.15-0.87) and were more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis. Conclusions and Relevance The findings suggest that individuals with prodromal or unrecognized Parkinson disease may have greater impairment in activities involving mobility and strength up to 3 years prior to diagnosis compared with the general population. Identification of prodromal disease may facilitate earlier intervention to improve function.
Rising Rates of Homicide of Children and Adolescents
Authors: Diane N. Haddad, Elinore J. Kaufman
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Single-Cell Analysis Reveals Transcriptomic Features of Drug-Tolerant Persisters and Stromal Adaptation in a Patient-Derived EGFR-Mutated Lung Adenocarcinoma Xenograft Model
Authors: Nadeem Moghal, Quan Li, Erin L. Stewart, Roya Navab, Masashi Mikubo, Elisa D’Arcangelo, Sebastiao N. Martins-Filho, Vibha Raghavan, Nhu-An Pham, Ming Li, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao
Journal: Journal of Thoracic Oncology (2022)

Targeted therapies require life-long treatment, as drug discontinuation invariably leads to tumor recurrence. Recurrence is mainly driven by minor subpopulations of drug-tolerant persister (DTP) cells that survive the cytotoxic drug effect. In lung cancer, DTP studies have mainly been conducted with cell line models.We conducted an in vivo DTP study using a lung adenocarcinoma patient-derived xenograft tumor driven by an EGFR mutation. Daily treatment of tumor-bearing mice for 5 to 6 weeks with the EGFR inhibitor erlotinib markedly shrunk tumors and generated DTPs, which were analyzed by whole exome, bulk population transcriptome, and single-cell RNA sequencing.The DTP tumors maintained the genomic clonal architecture of untreated baseline (BL) tumors but had reduced proliferation. Single-cell RNA sequencing identified a rare (approximately 4%) subpopulation of BL cells (DTP-like) with transcriptomic similarity to DTP cells and intermediate activity of pathways that are up-regulated in DTPs. Furthermore, the predominant transforming growth factor-β activated cancer-associated fibroblast (CAF) population in BL tumors was replaced by a CAF population enriched for IL6 production. In vitro experiments indicate that these populations interconvert depending on the levels of transforming growth factor-β versus NF-κB signaling, which is modulated by tyrosine kinase inhibitor presence. The DTPs had signs of increased NF-κB and STAT3 signaling, which may promote their survival.The DTPs may arise from a specific preexisting subpopulation of cancer cells with partial activation of specific drug resistance pathways. Tyrosine kinase inhibitor treatment induces DTPs revealing greater activation of these pathways while converting the major preexisting CAF population into a new state that may further promote DTP survival.
Corrigendum to “Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up”
Authors: E. Zucca, L. Arcaini, C. Buske, P.W. Johnson, M. Ponzoni, M. Raderer, U. Ricardi, A. Salar, K. Stamatopoulos, C. Thieblemont, A. Wotherspoon, M. Ladetto
Journal: Annals of Oncology (2022)
Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and meta-analysis
Authors: Bradley J. Langford, Jean-Paul R. Soucy, Valerie Leung, Miranda So, Angela T.H. Kwan, Jacob S. Portnoff, Silvia Bertagnolio, Sumit Raybardhan, Derek R. MacFadden, Nick Daneman
Journal: Clinical Microbiology and Infection (2022)

BackgroundCOVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises.ObjectiveWe aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings.Data sourceA search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022.Study eligibilityStudies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted.MethodsPooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed.ResultsOf 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67–1.47) or proportion (risk ratio 0.91, 95% CI: 0.55–1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92–2.92; risk ratio 1.08, 95% CI: 0.91–1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03–1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40).ConclusionThe COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.
PINK1/Parkin-mediated mitophagy in neurodegenerative diseases
Authors: Jie Li, Dongming Yang, Zhiping Li, Mengyang Zhao, Dongdong Wang, Zhixin Sun, Pei Wen, Yuexin Dai, Fengting Gou, Yilan Ji, Deming Zhao, Lifeng Yang
Journal: Ageing Research Reviews (2022)
Relationship of Atezolizumab plus Bevacizumab Treatment with Muscle Volume Loss in Unresectable Hepatocellular Carcinoma Patients: Multicenter Analysis
Authors: Atsushi Hiraoka, Takashi Kumada, Toshifumi Tada, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Naganuma, Masaki Kaibori, Takaaki Tanaka, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Yohei Koizumi, Shinichiro Nakamura, Kouji Joko, Hiroko Iijima, Hisashi Kosaka, Yoichi Hiasa, Masatoshi Kudo
Journal: Liver Cancer (2022)

There is no known report regarding the relationship of atezolizumab plus bevacizumab (Atez/Bev) treatment with muscle volume loss (MVL) in unresectable hepatocellular carcinoma (u-HCC) patients. This study aimed to elucidate the clinical relationship between MVL and Atez/Bev.From September 2020 to December 2021, 229 u-HCC patients treated with Atez/Bev and with muscle volume data obtained by computed tomography at the baseline available were analyzed (median age, 74 years; males, 186 (81.2%); ECOG PS 0/1, 221 (96.5%); HCV:HBV:alcohol:others = 81:33:40:75; Child-Pugh A, 212 (92.6%); modified albumin-bilirubin (mALBI) grade 1:2a:2b = 79:60:90; BCLC 0:A:B:C = 1:24:87:117; median observation period, 6.8 months). Japan Society of Hepatology criteria were used for definition of MVL and prognostic factors were retrospectively evaluated.Multivariate Cox-hazard analysis of prognostic factors for progression-free survival (PFS) showed elevated alpha-fetoprotein (AFP) (≥100 ng/mL) (HR 1.848, 95% CI 1.264-2.702, p = 0.002), mALBI grade (≥2a) (HR 1.563, 95% CI 1.035-2.359, p = 0.034), and MVL (HR 1.479, 95% CI 1.020-2.144, p = 0.039) as significant factors. For overall survival (OS), significant factors included elevated AFP (≥100 ng/mL) (HR 3.564, 95% CI 1.856-6.844, p < 0.001), mALBI grade (≥2a) (HR 3.451, 95% CI 1.580-7.538, p = 0.002), and MVL (HR 2.119, 95% CI 1.150-3.904, p = 0.016). Patients with MVL (MVL group, n = 91) showed worse PFS than those without (non-MVL group, n = 138) (median PFS 5.3 vs. 7.6 months, p = 0.025), while the MVL group showed worse OS (p = 0.038), though neither reached the median survival time.MVL may be a clinical factor related to poor prognosis in patients receiving Atez/Bev treatment for u-HCC.
What Is the Future of Factor XI Inhibitors?
Authors: Jeffrey I. Weitz, John W. Eikelboom
Journal: Circulation (2022)

arenteral and oral factor XI (FXI) inhibitors, the next potential generation of anticoagulants, are undergoing phase-3 evaluation with the hope that they will be safer than currently available agents. 1 This article (1) addresses the unmet needs in anticoagulation therapy; (2) explains why FXI may be more important for thrombosis than for hemostasis; (3) identifies the FXI inhibitors in advanced stages of development;(4) describes the results of the phase 2 trials; and (5) provides perspective on the opportunities and challenges for this new class of anticoagulants.
Crizotinib in Combination With Chemotherapy for Pediatric Patients With ALK+ Anaplastic Large-Cell Lymphoma: The Results of Children's Oncology Group Trial ANHL12P1
Authors: Eric J. Lowe, Anne F. Reilly, Megan S. Lim, Thomas G. Gross, Lauren Saguilig, Donald A. Barkauskas, Rui Wu, Sarah Alexander, Catherine M. Bollard
Journal: Journal of Clinical Oncology (2022)

Arm crizotinib (CZ) of the Children's Oncology Group trial ANHL12P1 (ClinicalTrials.gov identifier: NCT01979536) examined the efficacy and toxicity of adding CZ to standard chemotherapy for children with newly diagnosed, nonlocalized ALK+ CD30+ anaplastic large-cell lymphoma (ALCL).
Evaluation of Nanopore sequencing for Mycobacterium tuberculosis drug susceptibility testing and outbreak investigation: a genomic analysis
Authors: Michael B Hall, Marie Sylvianne Rabodoarivelo, Anastasia Koch, Anzaan Dippenaar, Sophie George, Melanie Grobbelaar, Robin Warren, Timothy M Walker, Helen Cox, Sebastien Gagneux, Derrick Crook, Tim Peto, Niaina Rakotosamimanana, Simon Grandjean Lapierre, Zamin Iqbal
Journal: The Lancet Microbe (2022)
Second-line levofloxacin-based quadruple therapy versus bismuth-based quadruple therapy for Helicobacter pylori eradication and long-term changes to the gut microbiota and antibiotic resistome: a multicentre, open-label, randomised controlled trial
Authors: Jyh-Ming Liou, Xiao-Tao Jiang, Chieh-Chang Chen, Jiing-Chyuan Luo, Ming-Jong Bair, Po-Yueh Chen, Chu-Kuang Chou, Yu-Jen Fang, Mei-Jyh Chen, Chien-Chuan Chen, Ji-Yuh Lee, Tsung-Hua Yang, Chien-Chun Yu, Chia-Chi Kuo, Min-Chin Chiu, Chi-Yi Chen, Chia-Tung Shun, Wen-Hao Hu, Min-Horn Tsai, Yao-Chun Hsu, Cheng-Hao Tseng, Chi-Yang Chang, Jaw-Town Lin, Emad M El-Omar, Ming-Shiang Wu, Chun-Ying Wu, Yi-Chia Lee, Ping-Huei Tseng, Jeng-Yih Wu, Chi-Ming Tai, Ching-Tai Lee, Wen-Lun Wang
Journal: The Lancet. Gastroenterology & hepatology (2022)
Intracellular Formation of Hemicyanine Nanoparticle Enhances Tumor‐Targeting Photoacoustic Imaging and Photothermal Therapy
Authors: Lele Zhang, Minghui Wang, Fangzheng Wu, Li Liu, Xingxing Ren, Zijuan Hai
Journal: Advanced Healthcare Materials (2022)

Alkaline phosphatase (ALP) is a tumor marker for early diagnosis and treatment. Tumor targeting can recognize and fight tumor cells more accurately from healthy cells. Glycyrrhetinic acid (GA) is a targeting ligand of liver tumors. Photoacoustic imaging (PAI) and photothermal therapy (PTT) are promising techniques for tumor diagnosis and treatment. The outstanding characteristics of Hemicyanine (HCy) dye make it suitable for tumor diagnosis and treatment. However, using HCy nanoparticle (HCy NP) for liver tumor-targeting PAI and PTT has not been reported. Herein, Probe-1 is developed to enhance PAI and PTT of liver tumors due to GA targeting and intracellular ALP-instructed self-assembly of HCy NP. Compared to Probe-2 without self-assembly ability, Probe-1 displays a 4.6-fold higher PAI signal or 1.7-fold lower half inhibitory concentrations in HepG2 cells. Moreover, Probe-1 shows extended retention time (10 vs 6 h) and 2.1-fold higher PAI signal than Probe-2 in HepG2 tumors. The HepG2 tumors in Group Probe-1 obviously increase 18 °C (Tmax : 55 °C) with a 3.3-fold decreased volume while that in Group Probe-2 mildly increase 9.8 °C (Tmax : 46.8 °C) with a 4.3-fold increased volume. It is envisioned that this smart self-assembly strategy can be easily adjusted for PAI and PTT of more tumors.
Methodological and reporting standards for quality-of-life data eligible for European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) credit
Authors: S.F. Oosting, J. Barriuso, A. Bottomley, M. Galotti, B. Gyawali, B. Kiesewetter, N.J. Latino, F. Martinelli, M. Pe, G. Pentheroudakis, F. Roitberg, H. Vachon, E.G.E. de Vries, M. Piccart, N.I. Cherny
Journal: Annals of Oncology (2022)

The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) has been developed to grade clinical benefit of cancer therapies. Improvement in quality of life (QoL) is considered relevant, especially in the non-curative setting. This is reflected by an upgrade of the preliminary ESMO-MCBS score if QoL is improved compared to the control arm or a downgrade if an improvement in progression-free survival is not paralleled by an improvement in QoL or overall survival. Given the importance of QoL for the final score, a need to ensure the robustness of QoL data was recognised.A checklist was created based on existing guidelines for QoL research. Field testing was carried out using clinical trials that either received an adjustment of the preliminary ESMO-MCBS score based on QoL or had QoL as the primary endpoint. Several rounds of revision and re-testing of the checklist were undertaken until a final consensus was reached.The final checklist consists of four items and can be applied if three prerequisites are met: (i) QoL is at least a secondary endpoint, (ii) evidence of reliability and validity of the instrument is provided, and (iii) a statistically and clinically significant improvement in QoL is observed. The four items on the checklist pertain to the (i) hypothesis, (ii) compliance and missing data, (iii) presentation of the results, and (iv) statistical and clinical relevance. Field testing revealed that a clear QoL hypothesis and correction for multiple testing were mostly lacking, while the main statistical method was always described.Implementation of the ESMO-MCBS QoL checklist will facilitate objective and transparent decision making on QoL data within the ESMO-MCBS scoring process. Trials published until 1 January 2025 will have to meet the prerequisites and at least two items for crediting QoL benefit in the final ESMO-MCBS score. Trials published thereafter will have to meet all four items.
Association of Circulating <scp>Antibody‐Secreting</scp> Cell Maturity With Disease Features in Primary Sjögren's Syndrome
Authors: Tobit D. Steinmetz, Gwenny M. Verstappen, Sebastian R. Schulz, Liseth de Wolff, Rick Wilbrink, Annie Visser, Janneke Terpstra, Hendrika Bootsma, Frans G. M. Kroese
Journal: Arthritis & Rheumatology (2022)

Objective B cell hyperactivity plays an important role in primary Sjögren's syndrome (SS). We undertook this study to better understand the B cell effector branch, namely antibody‐secreting cells (ASCs) in primary SS, and to examine the quantity, maturity, and inflammatory properties of ASCs in primary SS patients. Methods Circulating ASCs, defined as CD3–CD14–CD27+CD38++ cells, from 21 primary SS patients and 10 healthy controls were assessed using spectral flow cytometry. Expression levels of relevant ASC markers relating to maturity, survival, and inflammatory status were analyzed using a t‐distributed stochastic neighbor embedding approach. Correlation of ASC properties with primary SS disease parameters was assessed. Results ASCs were more abundant in peripheral blood from primary SS patients than from healthy controls (mean ± SD 3.1 ± 5.1 cells/μl versus 1.1 ± 1.0 cells/μl, respectively; P = 0.048) and displayed a more mature phenotype (mean ± SD CD19– ASCs 0.37 ± 1.21 cells/μl versus 0.06 ± 0.11 cells/μl, respectively; P = 0.005). An inflammatory CXCR3+ phenotype of ASCs correlated positively with our newly developed ASC maturity index (r = 0.568, P = 0.007) but correlated negatively with antiinflammatory interleukin‐10 expression (r = –0.769, P &lt; 0.001). ASCs with a higher maturity index also demonstrated higher levels of the pro‐survival protein myeloid cell leukemia 1 (r = 0.567, P = 0.007). Frequency and/or maturity of ASCs correlated with several primary SS disease parameters, such as antinuclear antibody and anti‐La/SSB titers, salivary gland focus scores, and ocular staining scores. Conclusion Quantity and maturity of ASCs in primary SS patients are increased and correlate with disease parameters. A higher maturity index of ASCs marks a pro‐survival and proinflammatory phenotype. Altogether, B cell hyperactivity in primary SS extends to the peripheral ASC compartment, raising potential for ASCs as future biomarkers or targets for primary SS treatment. image
Effect of Intensive Blood Pressure Control on Troponin and Natriuretic Peptide Levels: Findings From SPRINT
Authors: Jarett D. Berry, Haiying Chen, Vijay Nambi, Walter T. Ambrosius, Simon B. Ascher, Michael G. Shlipak, Joachim H. Ix, Rajesh Gupta, Anthony Killeen, Robert D. Toto, Dalane W. Kitzman, Christie M. Ballantyne, James A. de Lemos
Journal: Circulation (2022)

Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP.hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or <50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models.Randomization to intensive SBP lowering (versus standard SBP management) resulted in a 3% increase in hs-cTnT levels over 1-year follow-up (geometric mean ratio, 1.03 [95% CI, 1.01-1.04]) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47 [95% CI, 1.13, 1.90]). In contrast, randomization to intensive SBP lowering led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90 [95% CI, 0.87-0.93]) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57 [95% CI, 0.46-0.72]). The association of randomized treatment assignment on change in hs-cTnT was completely attenuated after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was completely attenuated after adjusting for change in SBP. Increases in hs-cTnT and NT-proBNP from baseline to 1 year were associated with higher risk for heart failure and death, with no significant interactions by treatment assignment.Intensive SBP lowering increased hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering decreased NT-proBNP, a finding that was explained by the decrease in SBP. These findings highlight the importance of noncardiac factors influencing variation in cardiac biomarkers and raise questions about the potential role of hs-cTnT as a surrogate marker for heart failure or death in SBP-lowering studies.